In treating chronic renal failure, various methods of purification and treatment of blood with machinery are used to replace the function of a healthy kidney. Such methods aim at withdrawing fluid and removing substances from the blood, and they may also involve adding fluid and substances to the blood. Such purification and treatment may be performed by pumping a dialysis fluid through a blood filtration unit, commonly denoted a dialyzer, in which fluid and substances are transported over a semi-permeable membrane. Diffusive mass transport through the membrane is predominant in hemodialysis (HD), whereas hemofiltration (HF) uses mainly convective mass transport through the membrane. Hemodiafiltration (HDF) is a combination of the two methods.
The withdrawal of fluid in the dialyzer, also known as ultrafiltration, is given by the difference between the spent dialysis fluid pumped out of the dialyzer and the fresh dialysis fluid pumped into the dialyzer. Because of the large volume of dialysis fluid that is exposed to the membrane in the dialyzer during a dialysis treatment, there is a need for accurate control of the ultrafiltration. Taking hemodialysis as an example, typically about 200 liters of dialysis fluid are passed through the dialyzer during a treatment session. The target amount of ultrafiltrate during a treatment session is typically about 2 to 3 liters and may need to be controlled with a maximum deviation of the order of only 0.1 to 0.2 liter. Accordingly, in this example, ultrafiltration may need to be controlled with a maximum error of approximately 1:1000 in relation to the total flow of dialysis fluid.
There are different prior art techniques for achieving accurate control of ultrafiltration in a dialysis apparatus.
U.S. Pat. No. 4,267,040 discloses a dialysis apparatus having a passive balancing device. The balancing device consists of two chambers, each being subdivided by a displaceable element and having an inlet line for fresh dialysis fluid and an outlet line connected to a drain for spent dialysis fluid. Cutoff valves driven and switched by a control unit are arranged in the inlet and outlet lines. A pump is provided between the dialyzer and the balancing device to convey the dialysis fluid. The balancing device is operated in such a way that fresh dialysis fluid is supplied from a dialysis fluid source to the two balancing chambers in alternation through appropriate switching of the cutoff valves in the inlet lines. At the same time, fresh dialysis fluid is supplied from an already filled space of the other balance chamber to the dialyzer. The spent dialysis fluid from the dialyzer is pumped into the second space of the same balance chamber, from which the spent dialysis fluid then goes into an outlet. The part of the liquid circuit enclosed between the balancing device and the dialyzer behaves like a closed, constant-volume system. The ultrafiltration in the dialyzer, i.e. the amount of fluid that passes from the blood side to the dialysis fluid side of the dialyzer membrane, is controlled by a dedicated filtration pump which is connected for controlled removal of fluid from the system.
A dialysis apparatus equipped with this type of balancing device has a number of disadvantages. For one, the switching of the balancing chambers may produce audible noise to the discomfort of the patient undergoing dialysis and also the caretakers. Audible noise may be highly undesirable in a clinic setting as well as in a home setting. Further, the cutoff valves that control the switching will be subjected to significant mechanical load over time and may start to leak dialysis fluid as result of wear and fatigue. Any such leaks will produce errors in the resulting ultrafiltration. Still further, errors in the dedicated filtration pump will have a significant impact on the accuracy of the ultrafiltration, and it may be necessary to take measures to carefully control and supervise the operation of the filtration pump.
In this context, DE69007342 discloses a technique for calibrating a filtration pump, which is a volumetric pump that has either a rotor or a diaphragm for displacing the dialysis fluid. The pump is equipped with a pulse generator which emits pulses that represent a certain angle of rotation of the rotor or a certain displacement of the diaphragm and correspond to a certain quantity of dialysis fluid. During regular operation, the flow rate of the filtration pump is determined by dead reckoning, i.e. by counting the number of pulses emitted and applying a known correspondence between the number of pulses and the quantity of liquid pumped. This correspondence is determined in a calibration procedure, in which the pumped liquid is switched into a reservoir of exactly known capacity. By counting the number of pulses emitted in order to fill the reservoir, the exact correspondence between the number of impulses emitted and the quantity of liquid pumped can be determined.
The prior art also comprises U.S. Pat. No. 4,747,950 which is designed to balance the flow of dialysis fluid into the dialyzer, generated by an upstream pump, with the flow of dialysis fluid out of the dialyzer, generated by a downstream pump, and to achieve ultrafiltration by withdrawing a controlled amount of dialysis fluid from a location either upstream or downstream of the dialyzer. The disclosed dialysis fluid supply system contains a large number of pumps, in addition to the upstream and downstream pumps, and involves a complex distribution of dialysis fluid between and within different receptacles in the system. To ensure a balanced flow, a calibration procedure is implemented, in which the dialyzer is temporarily by-passed such that the dialysis fluid is pumped from the upstream pump through a calibration chamber to the downstream pump. The calibration chamber has a sight tube allowing the level of dialysis fluid to be visually inspected. The flow rate of the upstream pump is controlled in relation to the flow rate of the downstream pump until the level of dialysis fluid remains at a constant level in the sight tube.
Other techniques for ultrafiltration control by balancing the flow rates of fresh and spent dialysis fluid are e.g. known from US2012/0193290, US2011/0132838, US2008/0105600, US2002/0088752, US2012/0279910 and US2010/0016777.
Another approach to control the ultrafiltration during dialysis is to install one or more pumps upstream of the dialyzer and one or more pumps downstream the dialyzer in the dialysis fluid supply system and to relatively control the flow rates of the upstream and downstream pumps to achieve a desired ultrafiltration rate. This type of control requires accurate and continuous measurements of the flow rates of dialysis fluid into and out of the dialyzer, and one or more advanced flow meters are installed in the dialysis fluid supply system to provide this information. An example of a flow meter capable of continuously measuring the difference between the dialysis fluid flows into and out of the dialyzer is known from U.S. Pat. No. 4,585,552. A dialysis apparatus based on this approach may produce significantly less audible noise than a dialysis device with a balancing device. Further, since the ultrafiltration is controlled based on the readings of one or more flow meters, ultrafiltration may be largely unaffected by leaks in the dialysis fluid supply system, as long as the flow meter(s) operate correctly. However, flow meters with the required accuracy and precision may be quite costly and complex. It is also vital that the flow meters operate correctly over a long time of use. Techniques for calibrating the flow meters in this context are e.g. known from U.S. Pat. No. 6,331,252 and US2012/0145615.
The prior art also comprises US2007/0243990 which is unrelated to ultrafiltration control and discloses an apheresis system in which blood is removed from a donor, directed to a blood component separation device, such as a centrifuge, which collects one or more blood components (e.g. red blood cells, white blood cells, platelets or plasma), whereupon the remainder is returned to the donor. US2007/0243990 proposes a calibration procedure for relatively calibrating pairs of pumps in the apheresis system. During the calibration procedure, the pumps are alternately activated so that one pump is operated to increase the fluid level in a reservoir from an initial level, and then the other pump is operated to decrease the fluid level back to the initial level in the reservoir. A pump volume ratio between the pumps is given by the number of strokes performed by the respective pump while filling and emptying the reservoir. The pump volume ratio is stated to be useful for increasing the effectiveness and efficiency of the donation process. Another technique for relative pump calibration in the context of apheresis for blood plasma filtering and/or platelet separation is known from U.S. Pat. No. 4,769,001.